The cause and mechanisms of injury in most chronic degenerative diseases of man are unknown. Over the last several years, evidence has accumulated that some chronic degenerative diseases of man are associated with slow or persistent viral infections. At present, there are available several animal models of persistent viral infection associated with chronic disease in which the pathogenesis of resultant tissue injury can be critically studied. Once mechanisms of injury and viral persistence are understood, rational approaches to treatment may be uncovered. Of these models, infection of mice with lymphocytic choriomeningitis (LCM) virus has proven a most illuminating and productive model to study. Investigation of persistent LCM virus infection has led to the understanding that (1) despite the initiation of life-long viral persistence following either nenonatal or in utero infection, the animal is able to mount both a humoral and cellular immune response against the virus and (2) interaction of virus with the anti-viral immune response is responsible for most of the tissue injury seen in chronic disease. This proposal studies how virus persists in the face of an anti-viral immune response and investigates the fate of such virus when complexed to anti-viral antibody and complement. Specifically, virus-anti viral antibody complexes themselves will be studied, their turnover time in the animal and their handling by macrophages and other body cells. Furthermore, the possibility of a blocking antibody as a cause for viral persistence and the possible role of an immune response gene in disease susceptibility will be evaluated.